Splenic quality control of Erythrocytes and natural Protection against malaria: a phenotype-genotype Interactions Approach in population (SEPIA)

Malaria due to Plasmodium falciparum, a potentially lethal parasitic disease, has selected human genetic polymorphisms modulating susceptibility to infection. In sub-Saharan Africa, Fulani people are more resistant to malaria than other ethnic groups. This phenotype is not explained by known genetic polymorphisms associated with natural resistance to malaria, such as the sickle cell trait or other polymorphisms related to red blood cells (RBCs) or immunity. Fulani have a lower susceptibility to malaria but a higher prevalence of anemia and splenomegaly compared to the other groups living in sympatry. In a recent field survey in North Benin, a significantly greater deformability of circulating RBCs in Fulani has been discovered than in non-Fulani, especially in case of recent infection with P. falciparum. This splenic hyper-reactivity of Fulani to malaria infection explains both the greater deformability of circulating RBC (by increased splenic clearance of rigid RBCs) and the anemia-splenomegaly association (by splenic congestion). Heritability analysis of the deformability of circulating RBCs in this study revealed a very strong genetic component in Fulani paving the way for the identification of a new genetic factor involved in natural resistance to malaria.

Genetics and Genomics
Immunology
Vulnerable Populations

Mar 2026 — Mar 2030

$850,695

Benin